The proposed research attempts to analyze T cell specificity and the nature of T receptors during ontogeny and at the level of effector T cells. The experimental models used are acute viral infections in mice, during which are generated virus-specific cytotoxic T cells that are restricted to Self-major histocompatibility antigens (Self-H) and whose activity can be tested in 51Cr release assays in vitro. The main questions studied are: 1. How does immunocompetence of T cells differentiate during ontogeny and how is specificity for Self-H and for foreign antigenic viral determinants acquired? Irradiation bone marrow chimeras and thymus chimeras are used to establish whether thymic selection of specificity for Self-H is sufficient for full T cell maturation or whether post-thymic T cell maturation is necessary. 2. What is the nature of the antigenic determinants recognized by T cells? Serologically distinct but related vesicular stomatitis viruses (VSV) are used to investigate T cell specificity for foreign antigens and H-2 mutants to analyze T cell specificity for Self-H. 3. How do immune response genes function? Are they expressed on antigen presenting cells or do they reflect defects in the repertoire? Sendai, VSV, vaccinia and lymphocytic choriomeningitis virus are used for the study of specificity of Ir genes. Immunofluorescence, cocapping studies and immune absorption or immune precipitation methods are employed to study events on antigen presenting target cells.